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作 者:HE Xi YANG Liu LIU Xintong WEI Wei SHI Ce LI Baoquan LI Jiang
机构地区:[1]Dental Hospital,Jilin University,Changchun 130021,P.R.China
出 处:《Chemical Research in Chinese Universities》2019年第3期418-426,共9页高等学校化学研究(英文版)
摘 要:Sjogren's syndrome(SS) is an autoimmune disease characterized as the impairment of salivary secretion mediated by abnormal aquaporin 5(AQP5). Here we used AQP5 promoter as the target to screen the eflective components from natural drugs. Panax quinquefolius and its specific ingredient, Rbl, were identified to increase the AQP5 transcriptional activity and AQP5 expression. Then we investigated the possibility of Rbl binding to sex hormone receptors and demonstrated that Rbl bound specifically to estrogen receptor alpha(ERa), but not to androgen receptor. Next, we found that ERa overexpression magnified the effect of Rbl induced AQP5 transcription, and the silence of ERa blocked this effect, demonstrating that Rbl activated AQP5 transcription via ERa pathway. Importantly, we constructed SS mouse model and investigated the effects of Rbl on salivary secretion in vivo. SS mice exhibited significant impairment in salivary secretion and decreased AQP5 expression in the submandibular gland. Intriguingly, SS mice administered with Rbl exhibited dramatically increased salivary secretion, followed by decreased diary water consumption. In particular, Rbl up-regulated AQP5 expression localized in the submandibular gland, almost similar to the SS mice administered with estrogen. Our data demonstrated that Rbl bound with ERa to up-regulate AQP5 to increase saliva secretion, thus functioned as a potential natural phytoestrogen for the therapy of salivary secretion impairment in SS patients.
关 键 词:Sjogren's syndrome AQUAPORIN 5 Estrogen receptor alpha Ginsenoside RBL SUBMANDIBULAR gland
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